IIBBA   05544
INSTITUTO DE INVESTIGACIONES BIOQUIMICAS DE BUENOS AIRES
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
The unfolded protein sensor UDP-Glc:glycoprotein glucosyltransferase is conserved in Caenorhabditis elegans and participates in ER stress tolerance, development and lifespan
Autor/es:
BUZZI, LUCILA INÉS; SIMONETTA, SERGIO H.; HERNANDEZ, EVELYN; PARODI, ARMANDO; CASTRO, OLGA A.
Lugar:
Los Angeles
Reunión:
Congreso; 18th International C elegans Meeting; 2011
Institución organizadora:
Universidad de California/ Genetics Society of America Conferences
Resumen:
The UDP-Glc:glycoprotein glucosyltransferase (UGT) is the key component of the glycoprotein folding quality control mechanism that takes place in the endoplasmic reticulum (ER). It behaves as a sensor of glycoprotein conformation as it exclusively glucosylates glycoproteins not displaying their native conformations. The addition of this glucose residue enables the interaction of folding intermediates with Calnexin/Calreticulin. An enzymatically active UGT is encoded by a single gene in Schizosaccharomyces pombe, Drosophila melanogaster, Trypanosoma cruzi and plants. There are two homologues coding for UGT-like proteins in Euteleostomi and in the genus Caenorhabditis. Both UGT homologues (HUGT1 and HUGT2) are expressed in human cells, the former but not the latter displayed GT activity and was upregulated under ER stress conditions. Bioinformatics analysis showed that in C.elegans there are two open reading frames (F48E3.3 and F26H9.8 hereinafter referred to as C. elegans uggt-1 and uggt-2 genes respectively) coding for UGT homologues. Here we report that C. elegans expresses an active UGT protein localized in the ER that is encoded by uggt-1 gene. We constructed transgenic worms carrying the uggt-1promoter::gfp construct and found that UGGT-1 is expressed in cells of the nervous system and is upregulated under ER stress. Real time PCR analysis showed that both uggt-1 and uggt-2 are expressed during the entire C. elegans life cycle but at very different levels, being uggt-2 expression at most 3 % of uggt-1. Depletion of UGGT-1 by RNA interference resulted in a reduced lifespan and that of UGGT-1 and UGGT-2 in a delay in development. We found that both CeUGGT-1 and CeUGGT-2 play a protecting role under ER stress conditions since worms arrested at L2/L3 stages, in conditions that produce the accumulation of unfolded glycoproteins.